DNA repair enzymes play a key role in maintaining the genonmic integrity of all living cells. They are responsible for detecting and excising the potentially mutagenic lesions that arise in DNA either spontaneously or via oxidative damage. Detailed, high-resolution X-ray crystal structures of these enzymes, and their DNA complexes, will provide a solid basis towards understanding the mechanistic and biologic ramifications of essential repair processes. The DNA repair enzyme that is the subject of this proposal is human uracil-DNA glycosylase (UDG), and we have collected several high-resolution (>2.0 E) data sets of both wild-type and mutant human UDG bound to uracil-containing duplex DNA at SSRL beamline 7-1. The determination of these structures revealed in atomic detail the basis for UDG specificity and suggested models for initial DNA damage detection.